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Pre-radiation therapy (RT) dental extraction of at-risk teeth is recommended to prevent osteoradionecrosis (ORN). Occasionally, patients are unable or unwilling to complete the dental extractions. Some authors have proposed a safe "window" immediately postradiation, but data are nonexistent. We evaluated the feasibility and safety of dental extractions postradiation (DEXPoRT). This single-institution, institutional review board−approved observational study enrolled patients with head and neck cancer (HNC) from January 2020 to September 2022. Eligibility included definitive and adjunctive RT, ³1 tooth was recommended for extraction and patient was unable or unwilling to proceed with pre-RT extractions for any reason. Patients were recommended DEXPoRT within 4 months of RT completion. The primary endpoint was the cumulative incidence of exposed alveolar bone noted by any practitioner at any time postextraction. The actuarial cumulative incidence of exposed bone (and confirmed osteoradionecrosis) was calculated using the Gray method, with death as a competing risk. Fifty patients (80% male, median age = 60 years; range 25-81 years) were enrolled. Histologic diagnosis was primarily squamous cell carcinoma (n = 48; 96%) of the oral cavity, larynx or hypopharynx (n = 48; 96%). RT was definitive for 32 and adjuvant for 18. Median of the mean oral cavity dose was 39.8 Gy (range 10.1-64.8 Gy). A total of 36 received concurrent chemotherapy. Of 50 patients, 20 (40%) were noncompliant with DEXPoRT and the remaining 30 underwent a median of 8.5 extractions (range 1-28) at a median of 64.5 days post-RT (range 13-152 days). The median follow-up from the end of RT for survivors was 25 months (interquartile range 17-34). The 2-year cumulative incidence of any exposed bone was 24% (95% confidence interval 12%-36%). The 2-year exposed bone incidence for those who underwent DEXPoRT was 40% (22%-58%) versus 0% (0-0%) for those who were noncompliant with DEXPoRT. Of the 12 who developed exposed bone, 4 resolved, 1 was lost to follow-up, and 7 were confirmed as ORN. Of the 7 with confirmed ORN, 2 died of cancer, 2 were treated conservatively, 1 underwent surgery, 1 received hyperbaric oxygen, and 1 received surgery and hyperbaric oxygen. Post-RT dental extractions incur significant risk, even if performed within a 4-month window. Further follow-up is required to determine whether any long-term benefits exist as compared with observation without extraction. [ABSTRACT FROM AUTHOR]

Importance: Nonrestorable teeth are recommended to be extracted prior to radiation therapy (RT). Occasionally, preradiation extractions introduce unacceptable delays in treatment initiation. Planned dental extractions immediately postradiation presents an alternative strategy, though outcomes are uncertain., Objective: To evaluate the feasibility and safety of dental extractions immediately postradiation., Design, Setting, and Participants: A prospective cohort study including patients planned for curative-intent RT but unable or unwilling to proceed with 1 or more extractions recommended pretreatment was carried out. From January 2020 to September 2022, 58 patients were screened and 50 enrolled. The dental care was performed at a single academic department and the cancer care at regional centers. Analysis took place between September 22, 2023, and June 10, 2024., Exposure: On completion of RT, patients were recommended to complete extractions as soon as feasible, and ideally within 4 months., Main Outcomes and Measures: The primary end point was the actuarial cumulative incidence of exposed alveolar bone noted by any practitioner at any time after extraction, calculated using Gray method with death as a competing risk. As a pilot study, no formal power calculation was performed; resources allowed for 50 evaluable patients., Results: Among the 50 participants enrolled, RT was nonoperative for 32 patients (64%) and postoperative for 18 patients (36%). Intensity-modulated RT (IMRT) was delivered in all patients. Of the 50 patients, 20 (40%) declined dental extractions immediately postradiation and the remaining 30 (60%) underwent a median (range) of 8.5 (1-28) extractions at a median (range) of 64.5 (13-152) days after RT. The median (IQR) follow-up for survivors without exposed bone was 26 (17-35) months from the end of RT. The 2-year cumulative incidence of any exposed bone was 27% (95% CI, 14%-40%). The 2-year incidence of exposed bone for those who underwent dental extractions immediately postradiation was 40% (95% CI, 22%-58%) and 7% (95% CI, 0%-22%) for those who did not. Of the 13 who developed exposed bone: 4 resolved, 1 was lost to follow-up, and 8 were confirmed as osteoradionecrosis., Conclusions and Relevance: This cohort study found that postradiation dental extractions incur considerable risk, even if performed within a 4-month window.

Background: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings., Methods: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events., Results: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%)., Conclusions: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.)., (Copyright © 2022 Massachusetts Medical Society.)

Historically, oncology clinical trials have focused on comparing a new drug's efficacy to the standard of care. However, as our understanding of molecular pathways in oncology has evolved, so has our ability to predict how patients will respond to a particular drug, and thus comparison with a standard therapy has become less important. Biomarkers and corresponding diagnostic testing are becoming more and more important to drug development but also limit the type of patient who may benefit from the therapy. Newer clinical trial designs have been developed to assess clinically meaningful endpoints in biomarker-enriched populations, and the number of modern, molecularly driven clinical trials are steadily increasing. At the same time, barriers to clinical trial enrollment have also grown. Many barriers contribute to nonenrollment in clinical trials, including patient, physician, institution, protocol, and regulatory barriers. At the protocol level, eligibility criteria have become a large roadblock to clinical trial accrual. Over time, eligibility criteria have become more and more restrictive. To accrue an adequate number of patients to molecularly driven trials, we should consider eligibility criteria carefully and attempt to reduce restrictive criteria. Reducing restrictive eligibility criteria will allow more patients to be eligible for clinical trial participation, will likely increase the speed of drug approvals, and will result in clinical trial results that more accurately reflect treatment of the population in the clinical setting.